Kidins220 and Aiolos promote thymic iNKT cell development by reducing TCR signals

• DOI: 10.1126/sciadv.adj2802
• Publication Date: 2024-03-15T17:58:37Z
• Authors: Laurenz A. Herr; Gina J. Fiala; Sagar; Anna-Maria Schaffer; Jonas F. Hummel; Marina Zintchenko; Katrin Raute; Rubí M.-H. Velasc...; Beate Heizmann; Karolina Ebert; Kerstin Fehrenbach; Iga Janowska; Susan Chan; Yakup Tanriver; Susana Minguet; Wolfgang W. Schamel
• Keywords: 0301 basic medicine; 03 medical and health sciences; Biomedicine and Life Sciences

Development of T cells is controlled by the signal strength TCR. The scaffold protein kinase D-interacting substrate 220 kilodalton (Kidins220) binds to TCR; however, its role in cell development was unknown. Here, we show that cell-specific Kidins220 knockout (T-KO) mice have strongly reduced invariant natural killer (iNKT) numbers and modest decreases conventional cells. Enhanced apoptosis due increased TCR signaling T-KO iNKT thymocytes developmental stages 2 3 shows down-regulates at these stages. scRNA-seq indicated transcription factor Aiolos down-regulated Kidins220-deficient Analysis an KO demonstrated a downstream effector during development. In periphery, upon stimulation with α-galactosylceramide, suggesting promotes peripheral Thus, reduces or dependent on stage.